Prediction of massive coronary thrombosis of the infarct-related artery in ST-elevation myocardial infarction.

Aim    To identify clinical, laboratory and angiographic predictors for development of massive coronary thrombosis in patients with ST-segment elevation myocardial infarction (STEMI).Material and methods    This prospective, single-site study included 137 patients with STEMI (mean age, 66.5±13.2 years). Among these patients, 59 were in the group of massive coronary thrombosis and 78 patients were in the group of minor thrombosis. To identify predictors for the development of massive coronary thrombosis, medical history data, blood count and biochemistry, coagulogram, and angiography data were analyzed. A predictive model was constructed using the method of binary logistic regression followed by a search for the optimum value of the prognostic function with a ROC analysis. Results    The study showed statistically significant roles of total bilirubin, platelets, prothrombin ratio (PTR), activated partial thromboplastin time (APTT), and presence of inferior myocardial infarction in prediction of massive coronary thrombosis in STEMI. The model sensitivity was 71.2 %, specificity 75.6 %, and overall diagnostic efficacy 73.7 %.Conclusion    The predictive model for the development of massive coronary thrombosis in STEMI based on laboratory and instrumental data potentially allows assessing the thrombus load in the infarction-involved coronary artery and determining the optimum tactics of percutaneous coronary intervention in patients with STEMI. This reduces the probability of distal embolization with fragments of the disintegrated thrombus and improves the prognosis of STEMI patients both during the stay in the hospital and in the long-term. According to results of this study, the prognostic model for massive coronary thrombosis in STEMI based on such indexes as the platelet count, PTR, APTT, total bilirubin, and presence of inferior myocardial infarction provides accurate predictions in 73.7 % of cases. Independent predictors of massive coronary thrombosis were inferior myocardial infarction and total bilirubin.

[Regional catheter thrombolysis for late proximal deep vein thrombosis]. / Rezul'taty lecheniya pozdnego proksimal'nogo tromboza glubokikh ven regionarnym kateternym trombolizisom.

OBJECTIVE: To compare the efficacy of regional catheter thrombolysis with urokinase and alteplase for late proximal deep vein thrombosis. MATERIAL AND METHODS: We analyzed safety and effectiveness of treatment of 38 patients with late proximal deep vein thrombosis divided into 2 statistically homogeneous groups by 19 people. In the first group, regional thrombolysis with urokinase was performed with injection of the drug into thrombosed popliteal, femoral and iliac veins. Alteplase was used in the second group. Patients received rivaroxaban in pre-, perioperative period and throughout 6 months after surgery. Complications of endovascular therapy were recorded. After 12 months, ultrasound and clinical examination were carried out to assess vein recanalization and venous outflow disorders. Vein recanalization was evaluated as follows: <50% - minimal, 50-99% - partial, 100% - complete. RESULTS: Minor hemorrhagic complications of endovascular treatment developed in 31.7 and 21% of patients, respectively. In the first group, complete vein recanalization occurred in 31.6%, partial - in 21%, minimal - in 47.4% of patients. In the second group, these values were 47.4%, 36.8% and 15.8%, respectively. In the first group, no signs of venous outflow disorders were observed in 31.6% of patients, mild disorders - in 15.8%, moderate disorders - in 31.6%, severe - in 21% of patients. In the second group, these values were 47.4%, 31.6%, 10.5% and 10.5%, respectively. CONCLUSION: Thrombolysis with alteplase is safer and more effective compared to urokinase.

[Pharmacomechanical thrombectomy for total-subtotal deep vein thrombosis]. / Farmakomekhanicheskaya trombektomiya v lechenii total'no-subtotal'nogo tromboza glubokikh ven.

OBJECTIVE: To improve treatment outcomes in patients with late stages of total-subtotal deep vein thrombosis using pharmacomechanical thrombectomy. MATERIAL AND METHODS: We compared treatment outcomes in 2 homogeneous groups of patients with deep vein thrombosis and severe acute venous insufficiency. Standard anticoagulation (apixaban) was performed in the first group (n=20), endovascular treatment was applied in the second group (n=20). Regional catheter thrombolysis was performed at the first stage, and percutaneous mechanical thrombectomy was performed at the second stage. Incidence of hemorrhagic syndrome was assessed. The results were evaluated after one year considering patency of deep veins and severity of venous outflow disorders. RESULTS: Hemorrhagic complications occurred in 15% and 25% of patients, respectively. This required discontinuation of anticoagulation throughout the treatment and subsequent appointment of minimum doses of apixaban. Complete restoration of vein patency was observed in 20% and 55%, partial recanalization - 45% and 25%, minimal recovery - in 35% and 20% of patients, respectively. In the first group, venous outflow disorders were absent in 20% of patients, mild disorders were registered in 45%, moderate - 20%, severe - 15% of patients. In the second group, these values were 55%, 25%, 20% and 0% of patients, respectively. CONCLUSION: Pharmacomechanical thromboectomy can improve treatment outcomes.

[Venous stenting in acute period of total and subtotal deep vein thrombosis]. / Effektivnost' venoznogo stentirovaniya v ostrom periode total'no-subtotal'nykh trombozov glubokikh ven.

OBJECTIVE: To study the efficacy and safety of venous stenting and long-term anticoagulation with inhibitors of blood clotting factor XA in the treatment of total and subtotal deep vein thrombosis. MATERIAL AND METHODS: We analyzed 60 patients with total and subtotal deep vein thrombosis divided into 2 comparable groups by 30 people. Patients of the first group underwent regional catheter thrombolysis and percutaneous mechanical thrombectomy. The same endovascular treatment supplemented by venous stenting was performed in the second group. In the first group, rivaroxaban was prescribed before, during and for 6 months after surgery; apixaban was used in the second group. Complications of endovascular and anticoagulant therapy were recorded. After 12 months, control ultrasound and clinical examination of patients was performed to analyze recanalization of deep veins and severity of venous outflow disorders. Recanalization of veins was evaluated as follows: less than 50% - minimal, 50-99% - partial, 100% - complete. RESULTS: In the first group, complete and partial recanalization of veins was found in 63.3 and 36.7% of patients, respectively. In the second group, these values were 93.3 and 6.7%, respectively. In the first group, venous outflow disorders were absent in 56.7%, mild violations presented in 36.6%, moderate violations - in 6.7% of patients. In the second group, venous outflow was normal in 93.3% of patients, and mild disorders presented in 6.7% of patients. Hemorrhagic complications developed in 8 (13.3%) patients, equally in both groups.

[Efficacy of percutaneous mechanical thrombectomy for proximal deep vein thrombosis]. / Effektivnost' chreskozhnoi mekhanicheskoi trombektomii pri lechenii proksimal'nogo tromboza glubokikh ven nizhnikh konechnostei.

OBJECTIVE: To study the efficacy and safety of percutaneous mechanical thrombectomy and long-term anticoagulation with rivaroxaban for proximal deep vein thrombosis. MATERIAL AND METHODS: We analyzed the effectiveness of treatment in 60 patients with proximal deep vein thrombosis divided into 2 homogeneous groups by 30 people. Standard therapy was performed in the first group, therapy with percutaneous mechanical thrombectomy was applied in the second group. Patients received rivaroxaban in preoperative, perioperative and 6-month postoperative period. We considered complications of endovascular treatment and anticoagulation. Ultrasound and clinical examination were carried out after 12 months to analyze restoration of deep vein patency and venous outflow disorders. Recovery of vein lumen was assessed as follows: <50% - minimal, 50-99% - partial, 100% - complete. RESULTS: Recurrent deep vein thrombosis was found in 2 (6.7%) patients of the second group. Hemorrhagic complications following rivaroxaban therapy occurred in 8 (13.3%) patients (equally in both groups). In the first group, complete restoration of vein lumen was found in 16.7% of patients, partial recovery - in 40%, minimal recovery - in 43.3% of patients. In the second group, these values were 16.7%, 60% and 23.3%, respectively. Severe venous outflow impairment developed in 43.3% of patients in the first group and 23.3% of patients in the second group. Moderate impairment occurred in 30% and 20% of patients, mild disorders - in 10% and 40% of patients, respectively. CONCLUSION: Percutaneous mechanical thrombectomy on the background of long-term anticoagulation with rivoroxaban improves treatment outcomes in patients with proximal deep vein thrombosis.

Formation and functionalization of Ge-nanoparticles in ZnO.

Semiconductor nanocrystals are often proposed as a viable route to improve solar energy conversion in photovoltaics and photoelectrochemical systems. Embedding the nanocrystals in, e.g. a transparent and conducting electrode of a solar cell will promote the photon absorption and subsequent transfer of the generated charge carriers from the nanocrystal, and thereby enhance the function of the electrode. This can be accomplished by embedding a semiconducting nanocrystal with a small bandgap in a transparent conducting oxide (TCO), which is commonly utilized as electrode in new generation solar cells. Here, we demonstrate the incorporation, formation, and functionalization of germanium (Ge) nanocrystals in zinc oxide utilizing ion implantation, where post implantation annealing at 800 °C results in diamond cubic Ge nanocrystals with sizes between 2 and 20 nm. Photoluminecence spectra show a distinct emission around 0.7 eV arising from the Ge nanocrystals, and with additional emission features up to 1.15 eV due to quantum confinement, demonstrating a novel functionalization and tunability of the TCO electrode.

[The no-Reflow Phenomenon During Primary Percutaneous Coronary Intervention in Patients With ST-Segment Elevation Myocardial Infarction due to Massive Coronary Thrombosis. Pathogenesis and Predictors of no-Reflow].

Despite successful and timely revascularization of the infarct-related artery, myocardial tissue remains underperfused in some patients. This condition is known as the no-reflow phenomenon, which is associated with a worse prognosis. The first part of the systematic review on no-reflow focuses on description of the no-reflow pathogenesis and predictors. This phenomenon has a complicated, multifactorial pathogenesis, including distal embolization, ischemic injury, reperfusion injury, and a component of individual predisposition. Meanwhile, this phenomenon undergoes spontaneous regression in some patients. Several studies have demonstrated the role of definite biomarkers and clinical indexes as risk predictors for no-reflow. The significance of each pathogenetic component of no-reflow is suggested to be different in different patients, which may warrant an individualized approach in the treatment.

[One-year results of conservative and endovascular treatment of deep venous thrombosis followed by severe acute venous insufficiency]. / Odnoletnie rezul'taty konservativnogo i endovaskulyarnogo lecheniya tromboza glubokikh ven s razvitiem tyazheloi ostroi venoznoi nedostatochnosti.

OBJECTIVE: To compare the results of conservative and endovascular treatment of deep vein thrombosis followed by acute severe venous insufficiency. MATERIAL AND METHODS: Two statistically valid groups of patients with deep vein thrombosis and acute severe venous insufficiency were compared. Warfarin was administered in the first group, endovascular methods - in the second group (n=30). At the first step, we performed catheter-guided thrombolysis, then transcutaneous mechanical thrombectomy and venous stent deployment. Anticoagulation was achieved with Apixaban. Hemorrhagic complications were monitored during the treatment. One-year results were assessed considering lumen patency restoration and severity of venous congestion with Villalty score. RESULTS: In the first group, each third patient had hemorrhagic complications that required cessation of anticoagulant therapy in 1.3% of patients. In the second group, hemorrhagic events occurred in 10% of patients and were managed by lowering Apixaban dosage. Complete restoration of lumen patency was detected in 23.3% in the first group and 93.3% in the second group. Partial restoration developed in 63.3% and 6.7%, occlusion in 13.3% and 0%, respectively. Only 23.3% of patients in the first group had no clinical evidence of venous congestion. Mild congestion was found in 20%, severe - in 56.7% of cases. In the second group, 6.7% of patients had minimal venous congestion.

[Efficacy of apixaban in prevention of haemorrhagic complications in treatment of deep vein thromboses with endovascular techniques]. / Éffektivnost' apiksabana v profilaktike gemorragicheskikh oslozhnenii pri lechenii trombozov glubokikh ven éndovaskuliarnymi tekhnologiiami.

PURPOSE: This study was undertaken to investigate efficacy of apixaban in prevention of haemorrhagic complications during treatment of proximal thromboses of deep veins of the lower extremities using endovascular techniques. PATIENTS AND METHODS: We retrospectively studied the results of treating a total of 50 patients presenting with deep vein thromboses at late stages of the pathological process. The patients were subdivided into 2 statistically homogeneous groups. Group One was composed of 30 patients undergoing treatment consisting in a combination of catheter-guided thrombolysis with urokinase and percutaneous mechanical thrombectomy, with rivaroxaban used for prolonged anticoagulation therapy. Group Two comprised 20 patients subjected to similar endovascular treatment with additional venous stenting. Prolonged 6-month anticoagulation therapy was carried out with apixaban. The results of treatment were assessed after 12 months by means of control ultrasonographic and clinical examination in order to determine the degree of restoration of the lumen of deep veins and severity of venous outflow impairments. RESULTS: After 1 year, in Group One patients there was no evidence of impaired venous outflow in 40% of patients, with a mild degree revealed in 40%, moderate degree in 13.3%, and severe degree in 6.7% of patients. In Group Two patients, there were no symptoms of venous insufficiency in 83.4%, with a mild degree revealed in 16.6%. Neither moderate nor severe impairments of venous outflow were observed. In Group One, manifestations of haemorrhagic syndrome on the background of taking rivaroxaban were noted to occur in 10% of patients and in Group Two on the background of taking apixaban also in 10% of patients. CONCLUSION: The use of apixaban in patients with proximal thromboses of deep veins of lower limbs on the background of treatment by endovascular techniques proved effective and safe.

[Case of effective endovascular treatment of venous gangrene]. / Sluchai éffektivnogo éndovaskuliarnogo lecheniia venoznoi gangreny.

Presented in this article is a clinical case report regarding treatment of a patient with deep vein thrombosis complicated by venous gangrene having developed 10 days after the onset of the disease. Conservative therapy (infusion of colloids and crystalloids, anticoagulants, agents improving microcirculation, venotonics, nonsteroidal anti-inflammatory drugs, elevated position of the limb) made it possible to stabilize the patient's condition, but not improving haemodynamics of the affected limb. A decision was made to use endovascular techniques. Treatment was carried out in three stages. The first stage during 48 hours consisted in regional catheter thrombolysis with urokinase, exerting a minimal clinical effect. The second stage was percutaneous mechanical thrombectomy after which the diameter of thrombosed veins became free by half, with the beginning of disease regression. The third stage consisted in venous stenting of residual stenosis of the iliac vein, resulting in normalization of the venous outflow from the affected limb. A conclusion was drawn on feasibility of combined use of regional thrombolysis, percutaneous mechanical thrombectomy, and venous stenting in treatment of venous gangrene.

[Choice of an alternative access in failed endovascular intervention through the right radial artery]. / Vybor al'ternativnogo dostupa pri neudache éndovaskuliarnogo vmeshatel'stva cherez pravuiu radial'nuiu arteriiu.

The transradial access has deservedly become the 'gold standard' while performing various X-ray endovascular interventions both diagnostic and therapeutic ones. However, along with all its advantages, it is not without disadvantages. These difficulties for the most part are related to peculiarities of the anatomy of upper-limb arteries. It is exactly complex anatomy that is the most common cause of complications and compelled change of the access while using the right radial artery. The purpose of our study was to examine the symmetry of complex anatomy of upper-limb arteries in order to choose an optimal and safe way of conversion of the access in case of forced refusal from the right radial access. For this reason there was developed an open multicentre registry acronymized as COMPAAS (COMPlex Anatomy of Arteries and Symmetry). During the work of this Registry from February to December 2018, correspondents of the study became 35 colleagues from 23 clinics of 11 cities of Russia. The working group analysed a total of 127 patients presenting with 157 variants of complex anatomy of lower limb arteries: high bifurcation of the radial artery (84), complete loop or tortuosity (66), and compartmental calcification of brachial arteries (7). The anatomy of arteries on the opposite upper extremity was studied based on angiographic findings. The most frequent variant (84 cases) of complex anatomy was high bifurcation of the radial artery at the level of the a. brachialis (20.9% of cases), with the origin of the brachial artery at the level of the a. axillaris being revealed half as often (9.9%). The maximum percentage of symmetry was observed in the group of patients presenting with compartmental calcification of upper-limb arteries (85.7%). Complete loop or marked (more than 100°) tortuosity of arteries on both arms was revealed in 54% of cases. Besides, in 25% of cases, tortuosity was combined with the high origin of the radial artery. It is noteworthy that none of the 127 patients appeared to have complex anatomy on the a. ulnaris. When revealing pronounced calcification of arteries of the forearm or a combination of high bifurcation with tortuosity, it seems feasible to decide upon conversion of the access to the femoral one (a. femoralis) or ulnar (a. ulnaris). In isolated high bifurcation on the right, effective conversion to the contralateral (left) radial approach is possible in not less than 75% of cases.

Monitoring selective etching of self-assembled nanostructured a-Si:Al films.

Nanoporous and nanowire structures based on silicon (Si) have a well recognized potential in a number of applications such as photovoltaics, energy storage and thermoelectricity. The immiscibility of Si and aluminum (Al) may be utilized to produce a thin film of vertically aligned Al nanowires of 5 nm diameter within an amorphous silicon matrix (a-Si), providing a cheap and scalable fabrication method for sub 5 nm size Si nanostructures. In this work we study functionalization of these structures by removal of the Al nanowires. The nanowires have been etched by an aqueous solution of HCl, which results in a structure of vertically aligned nanochannels in a-Si with admixture of SiO x . The removal of Al nanowires has been monitored by several electron microscopy techniques, x-ray diffraction, Rutherford backscattering spectroscopy, and optical reflectance. We have established that optical reflectance measurements can reliably identify the complete removal of Al, confirmed by other techniques. This provides a robust and relatively simple method for controlling the nano-fabrication process on a macroscopic scale.

[Results of administering oral anticoagulants for treatment of patients with venous thromboembolic complications]. / Rezul'taty primeneniia peroral'nykh antikoaguliantov pri lechenii bol'nykh s venoznymi tromboémbolicheskimi oslozhneniiami.

The objective of the study was to compare safety and efficacy of rivaroxaban and dabigatran with warfarin in treatment of patients with acute venous thromboembolic complications (VTEC). The authors analysed the results of examining and treating a total of 95 patients presenting with VTEC and randomly divided into three groups. In all groups the initial anticoagulant therapy consisted in unfractionated heparin administered for 5 days, after which the patients followed by switching were switched to a 6-month course of treatment with oral anticoagulants. Patients from Group One received warfarin, Group Two patients were treated with dabigatran etexilate, and Group Three patients were treated with rivaroxaban. Relapses of the disease were diagnosed in 2 (5.7%) patients from Group One. Haemorrhagic complications were noted in 8 (22.9%) Group One patients, in 3 (10%) Group Two patients and in 2 (6.7%) Group Three patients. After the end of treatment, complete recanalization of the thrombosed veins was revealed 13 (37.1%) patients from Group One, in 15 (50%) patients from Group Two and in 14 (46.7%) patients from Group Three. One year after the end of treatment, freedom from chronic venous insufficiency was observed in 8 (23.3%) patients of Group One, in 12 (40%) patients of Group Two and in 11 (36.6%) patients of Group Three. The composite quality of life indices after the treatment course were (appeared to be) higher in Group Two and Three patients compared with those of Group One. Hence, a conclusion was drawn that dabigatran and rivaroxaban turned out to be superior by efficacy and safety to warfarin in treatment of this patient cohort. No statistically significant differences were observed while comparing dabigatran and rivaroxaban.

Impurity sublattice localization in ZnO revealed by Li marker diffusion.

Sublattice localization of impurities in compound semiconductors, e.g., ZnO, determines their electronic and optical action. Despite that the impurity position may be envisaged based on charge considerations, the actual localization is often unknown, limiting our understanding of the incorporation and possible doping mechanisms. In this study, we demonstrate that the preferential sublattice occupation for a number of impurities in ZnO can be revealed by monitoring Li diffusion. In particular, using ion implantation, the impurity incorporation into the Zn sublattice (holds for, B, Mg, P, Ag, Cd, and Sb) manifests in the formation of Li-depleted regions behind the implanted one, while Li pileups in the region of the implantation peaks for impurities residing on O sites, e.g., N. The behavior appears to be of general validity and the phenomena are explained in terms of the apparent surplus of Zn and O interstitials, related to the lattice localization of the impurities. Furthermore, Cd+O and Mg+O co-doping experiments revealed that implanted O atoms act as an efficient blocking "filter" for fast diffusing Zn interstitials.

Tuning heterogeneous ion-radiation damage by composition in NixFe1-x binary single crystals.

Radiation-induced heterogeneous damage is the single largest source of failures seen in structural components in nuclear power reactors. Single crystal materials without grain boundaries, show considerable promise for overcoming this problem. In this work, such heterogeneous damage was further overcome in NixFe1-x single crystal alloys via a simple strategy of fine-tuning the composition. [001] NixFe1-x (x = 0, 0.38 and 0.62 at%) single crystals prepared using the Bridgman method were irradiated over a wide fluence range (4 × 1013 to 4 × 1015 ions per cm2). The irradiation-induced defect evolution was studied using Rutherford backscattering/channeling spectrometry, Monte Carlo simulations, transmission electron microscopy and nanoindentation. The results indicate an increased radiation tolerance of Ni0.38Fe0.62 compared to pure Ni and Ni0.62Fe0.38. The structural analysis performed by transmission electron microscopy revealed that defects tend to agglomerate at one place in Ni and Ni0.62Fe0.38, while in Ni0.38Fe0.62 no defect accumulation zone (characteristic damage peak) has been captured either at low or high fluence. Moreover, we found that the hardness change with the increase of Fe content is due to different arrangements of Fe atoms in the crystal structure, which influences the obtained mechanical properties of NixFe1-x in the pristine state and after ion implantation.

Discriminative stimulus effects of ethanol and 3 alpha-hydroxy-5 alpha-pregnan-20-one in relation to menstrual cycle phase in cynomolgus monkeys (Macaca fascicularis).

The present study was designed to characterize the discriminative stimulus effects of ethanol and the neurosteroid 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone) in nonhuman primates as a function of menstrual cycle phase. Female cynomolgus monkeys (Macaca fascicularis) were trained in a two-lever procedure to discriminate 1.0 g/kg ethanol (IG, 30 min pretreatment) from water using food reinforcement. A cumulative dosing procedure was used to assess changes in the potency of ethanol and an endogenous anxiolytic steroid in the follicular versus the luteal phase of the menstrual cycle. Plasma progesterone and allopregnanolone levels were determined within 24 h of testing to verify phase of menstrual cycle. The monkeys were more sensitive to the discriminative stimulus effects of ethanol and the ethanol-like effects of the endogenous neuroactive steroid allopregnanolone during the luteal phase of the menstrual cycle. These findings suggest that changes in the endogenous levels of ovarian-derived progesterone and allopregnanolone alter sensitivity to the discriminative stimulus effects of ethanol.

Characterization of the discriminative stimulus effects of GABA(A) receptor ligands in Macaca fascicularis monkeys under different ethanol training conditions.

RATIONALE: The current study was designed to extend our knowledge of the GABA(A) receptor system in mediating discriminative stimulus effects of ethanol in non-human primates. OBJECTIVES: To characterize the discriminative stimulus effects of ethanol, pentobarbital, midazolam, muscimol and morphine in male and female monkeys under different ethanol training conditions. METHODS: Adult male (n=8) and female (n=10) Macaca fascicularis monkeys were divided into four groups and trained to discriminate 1.0 g/kg ethanol (n=8) versus water or 2.0 g/kg ethanol (n=10) versus water in a 2x2 design with training dose and sex as main group factors. Solutions were administered intragastrically (20% ethanol w/v) and responding was maintained under a fixed-ratio schedule of food reinforcement. Dose-response determinations of ethanol, pentobarbital, midazolam, muscimol and morphine were made under the training condition of 30 min pretreatment interval. The ethanol pretreatment interval in training sessions was then increased to 60 min and the effects of ethanol, pentobarbital and midazolam were redetermined. RESULTS: Training dose influenced the ED50 of ethanol to produce substitution under both pretreatment intervals and pentobarbital to produce substitution under the 30-min pretreatment training interval. There were no group differences in sensitivity to midazolam. The potency of the ligands to produce ethanol substitution was consistent across groups with midazolam>pentobarbital>ethanol. There were no sex differences in substitution of the ligands for ethanol. Blood ethanol concentrations at the onset of ethanol training sessions were higher in the 2.0 g/kg groups and under longer pretreatment times, but were not different on the basis of sex. CONCLUSIONS: Pentobarbital and midazolam produce ethanol-like discriminative stimulus effects in male and female cynomolgus monkeys suggesting a significant GABA(A) component mediating the behavioral effects of ethanol. There was limited evidence that training dose of ethanol influenced substitution pattern of the GABA(A) ligands in cynomolgus monkeys, unlike previous findings in rats. Finally, there appear to be no sex differences in the profile of GABA(A) mechanisms involved in the discriminative stimulus effects of ethanol.

Ethanol-like discriminative stimulus effects of the neurosteroid 3 alpha-hydroxy-5 alpha-pregnan-20-one in female Macaca fascicularis monkeys.

The present study was designed to characterize the discriminative stimulus effects of ethanol and the neurosteroid 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone) in non-human primates. Female cynomolgus monkeys (Macaca fascicularis) were trained in a two-lever procedure to discriminate 1.0 g/kg ethanol (IG, 30 min pretreatment) from water using food reinforcement. Consistent with previous results in a variety of species, pentobarbital (0.56-17 mg/kg, IG) resulted in a dose-dependent substitution for the discriminative stimulus effects of ethanol, with an average ED50 value of 1.9 mg/kg. Administration of allopregnanolone (0.3-5.6 mg/kg, IV) also produced complete substitution for the discriminative stimulus effects of ethanol, with an ED50 value of 1.0 mg/kg. Plasma allopregnanolone levels 35 min following the administration of 3.0 mg/kg allopregnanolone ranged from 33 to 69 ng/ml. The ethanol-like discriminative stimulus effects of 1.0 mg/kg allopregnanolone (IV) were present for 60 min, with a return to complete water-appropriate responding at 90 min post-treatment. The results indicate that the endogenous neuroactive steroid allopregnanolone produces subjective effects in cynomolgus monkeys that are similar to ethanol. These findings suggest that changes in the endogenous levels of allopregnanolone could alter sensitivity to the subjective effects of ethanol.

Mesolimbic neuronal activity across behavioral states.

A goal of neurophysiology of the mesolimbic system is to determine the activity patterns within the regions in the prefrontal cortex, ventral neostriatum, and amygdala that regulate behavioral patterns to seek rewards. A new technology has been introduced in which arrays of microwires are implanted in different brain regions while activity patterns of ensembles of neurons are recorded for long periods of time during freely moving behaviors. Multichannel instrumentation and software is used for data acquisition and analysis. An initial hypothesis was that neural signals would be encountered in the nucleus accumbens and associated regions specifically related to reward. However, an initial study of neural activity and behavioral patterns during a simple lever press for intravenous cocaine (1 mg/kg) revealed that phasic excitatory or inhibitory neural activity patterns often appear prior to the reward phase. Individual neurons throughout the mesolimbic system appear to code information specific to sensory and motor events, tones, or lever presses in the chain of tasks leading to all rewards so far studied. Different spatial temporal patterns also appear within the same neural populations, as reward is changed from injected cocaine to heroin, from ingested pure water to ethanol in water or sucrose. Overall, patterns of activity for each neuron are found to shift dynamically during the operant task as changes are made in the target reward. Significant shifts in activity of mesolimbic neurons that are unrelated to specific sensory-motor events also appear during complex sessions, such as during a bout of ethanol consumption to reach satiation or during progressive ratio tasks with increasing difficulty. An emerging hypothesis is that some candidate neural elements in the mesolimbic system code the anticipated reward, whereas others serve internal logic functions of motivation that mediate extinction or resumption of specific goal-directed behaviors.

Effects of atrial natriuretic peptide on acute and chronic effects of morphine.

Atrial natriuretic peptide (ANP) is known to participate in different vegetative functions. The aim of the present study was to investigate the influence of ANP on nociception itself, pain sensitivity to morphine, and the development of acute and chronic tolerance to morphine. Morphine withdrawal signs were also evaluated by injecting naloxone. In adult, male NMRI mice, ANP administered SC or ICV did not affect pain sensitivity itself in a heat-radiant tail-flick test. Peptide treatment, however, depressed the acute nociceptive effect of a single dose of morphine (4 mg/kg, SC) after both SC (20-200 ng/animal) and ICV (5, 10, 20, or 200 ng/animal) ANP administration. ANP given SC and ICV attenuated the development of acute morphine tolerance. Acute morphine tolerance was assessed by giving a bolus injection of morphine (60 mg/kg) 24 h before the pain sensitivity to a challenge dose of morphine (4 mg/kg) was measured. ICV treatment with ANP also blocked the development of chronic morphine tolerance, but did not affect the appearance of naloxone-precipitated withdrawal syndromes. ANP seems to act differently on the development of tolerance to and dependence upon morphine.